ARC Future Fellow
Adelaide Medical School
Faculty of Health and Medical Sciences
Professor Michael Samuel
Head, Tumour Microenvironment Laboratory
Qualifications: BSc(Hons.) ANU, PhD Melb
Centre for Cancer Biology
SA Pathology, University of South Australia
Adelaide SA 5000, Australia.
The Beatson Institute for Cancer Research, Glasgow, United Kingdom
Many key characteristics of the tissue microenvironment are fundamentally changed in cancer, yielding the tumour microenvironment. Some of these changes arise as a result of tumours co-opting and modifying features of the tissue microenvironment to facilitate their growth.
Our research seeks to identify the mechanisms by which tumours remodel their microenvironments to promote tumour progression, with a view to uncovering new approaches to interfering with this process.
The Rho-ROCK signalling pathway is known to regulate the contractility of the cellular actomyosin cytoskeleton to promote tumour cell migration and invasion. Less well-understood is its role in remodelling the tissue microenvironment. We have discovered that activation of the ROCK kinase causes over-production and abnormal remodelling of collagen and other ECM components in many tissues. The resulting increase in tissue density disrupts normal tissue homeostasis and promotes tumourigenesis. We research the mechanisms downstream of ROCK that regulate these processes in both health and disease, with a focus on cancer.
Current research projects
- The molecular mechanisms by which the Rho-ROCK pathway promotes enhanced mechano-reciprocity and tumour progression
- How does the Rho-ROCK pathway generate a tumour-permissive immune microenvironment?
- How is the Rho-ROCK pathway regulated during wound healing and cancer progression?
- Identifying novel negative regulators of mechano-reciprocity.
S. T. Boyle, V. Poltavets, J. Kular, N. T. Pyne, J. J. Sandow, A. C. Lewis, K. J. Murphy, N. Kolesnikoff, P. A. B. Moretti, M. N. Tea, V. Tergaonkar, P. Timpson, S. M. Pitson, A. I. Webb, R. J. Whitfield, A. F. Lopez, M. Kochetkova and M. S. Samuel. "ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism". Nature Cell Biology 22(7):882-895 (2020).
S. T. Boyle, J. Kular, M. Nobis, A. Ruszkiewicz, P. Timpson and M. S. Samuel. "Acute compressive stress activates RHO/ROCK-mediated cellular processes". Small GTPases 11(5):354-370 (2020).
M. Z. Johan and M. S. Samuel. "Rho-ROCK signaling regulates tumour-microenvironment interactions". Biochem. Soc. Trans. 41(1):101-108 (2019).
H. A. Neubauer, M. N. Tea, J. R. Zebol, B. L. Gliddon, C. Stefanidis, P. A. B. Moretti, M. R. Pitman, M. Costabile, J. Kular, B. W. Stringer, B. W. Day, M. S. Samuel, C. S. Bonder, J. A. Powell and S. M. Pitson. Cytoplasmic dynein regulates the subcellular localization of sphingosine kinase 2 to elicit tumor-suppressive functions in glioblastoma. Oncogene 38(8):1151-1165 (2019).
V. Poltavets, M. Kochetkova, S. M. Pitson and M. S. Samuel. "The role of the extra-cellular matrix and its molecular and cellular regulators in cancer cell plasticity". Frontiers in Oncology 8:431 (2018).
A. S. Cazet, M. N. Hui, B. L. Elsworth, S. Z. Wu, D. Roden, C. L. Chan, J. N. Skhinas, R. Collot, J. Yang, K. Harvey, M. Z. Johan, C. Cooper, R. Nair, D. Herrmann, A. McFarland, N. Deng, M. Ruiz-Borrego, F. Rojo, J. M. Trigo, S. Bezares, R. Caballero, E. Lim, P. Timpson, S. O'Toole, D. N. Watkins, T. R. Cox, M. S. Samuel, M. Martín and A. Swarbrick. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat. Commun. 9(1):2897 (2018).
N. Rath, J. P. Morton, L. Julian, L. Helbig, S. Kadir, E. J. McGhee, K. I. Anderson, G. Kalna, M. Mullin, A. V. Pinho, I. Rooman, M. S. Samuel and M. F. Olson. "ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth". EMBO Mol Medicine 9(2):198-218 (2017).
C. Vennin, V. T. Chin, S. C.Warren, M. C. Lucas, D. Herrmann, A. Magenau, P. Melenec, S. N. Walters, G. Del Monte-Nieto, J. R. Conway, M. Nobis, A. H. Allam, R. A. McCloy, N. Currey, M. Pinese, A. Boulghourjian, A. Zaratzian, A. A. Adam, C. Heu, A. M. Nagrial, A. Chou, A. Steinmann, A. Drury, D. Froio, M. Giry-Laterriere, N. L. Harris, T. Phan, R. Jain, W. Weninger, E. J. McGhee, R. Whan, A. L. Johns, J. S. Samra, L. Chantrill, A. J. Gill, M. Kohonen-Corish, R. P. Harvey, A. V. Biankin; Australian Pancreatic Cancer Genome Initiative (APGI), T. R. Evans, K. I. Anderson, S. T. Grey, C. J. Ormandy, D. Gallego-Ortega, Y. Wang, M. S. Samuel, O. J. Sansom, A. Burgess, T. R. Cox, J. P. Morton, M. Pajic and Timpson P. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med. 9(384):eaai8504 (2017).
M. S. Samuel, N. Rath, S. F. Masre, S. T. Boyle, D. A. Greenhalgh, M. Kochetkova, S. Bryson, D. Stevenson and M. F. Olson. "Tissue-selective expression of a conditionally-active ROCK2-estrogen receptor fusion protein". Genesis 54(12):636-646 (2016).
S. T. Boyle and M. S. Samuel. "Mechano-reciprocity is maintained between physiological boundaries by tuning signal flux through the Rho-associated protein kinase". Small GTPases 7(3): 139-146 (2016).
J. Kular, K. G. Scheer, N. T. Pyne, A. H. Allam, A. Pollard, A. Magenau, R. Wright, N, Kolesnikoff, P. A. Moretti, L. Wullkopf, F. Stomski, A. J. Cowin, J. M. Woodcock, M. A. Grimbaldeston, S. M. Pitson, P. Timpson, H. S. Ramshaw, A. F. Lopez and M. S. Samuel. "A negative regulatory mechanism involving 14-3-3ζ limits signaling downstream of ROCK to regulate tissue stiffness in epidermal homeostasis." Developmental Cell 35(6): 759-774 (2015).
K. H. Yip, N. Kolesnikoff, C. Yu, N. Hauschild, H. Taing, L. Biggs, D. Goltzman, P. A. Gregory, P. H. Anderson, M. S. Samuel, S. J. Galli, A. F. Lopez and M. A. Grimbaldeston. "Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation." J Allergy Clin Immunol 133: 1356-1364.e14. (2014).
S. J. Ibbetson, N. T. Pyne, A. N. Pollard, M. F. Olson, M. S. Samuel. "Mechanotransduction Pathways Promoting Tumor Progression Are Activated in Invasive Human Squamous Cell Carcinoma." Am J Pathol. 183: 931-938 (2013).
M. S. Samuel , J. I. Lopez, E. J. McGhee, D. R. Croft, D. Strachan, P. Timpson, J. Munro, E. Schroder, J. Zhou, V. G. Brunton, N. Barker, H. Clevers, O. J. Sansom, K. I. Anderson, V. M. Weaver and M. F. Olson. "Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth." Cancer Cell 19: 776-791. (2011).
Year Citation 2018 Ramshaw, H., Kular, J., & Samuel, M. (2018). Wound Healing and the Non-cellular Microenvironment. In K. Turksen (Ed.), Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects (pp. 79-87). New Jersey, USA: John Wiley & Sons.
2012 Martemyanov, K. A., Parameswaran, P., Aligianis, I., Handley, M., Gual-Soler, M., Taguchi, T., . . . Lau, K. (2012). ROCK Kinases. In Encyclopedia of Signaling Molecules (pp. 1686-1690). Springer New York.
2012 Martemyanov, K. A., Parameswaran, P., Aligianis, I., Handley, M., Gual-Soler, M., Taguchi, T., . . . Lau, K. (2012). RAS (H-, K-, N-RAS). In Encyclopedia of Signaling Molecules (pp. 1596-1601). Springer New York.
2011 Samuel, M., & Olson, M. (2011). Rho-GTPases in Embryonic Stem Cells. In M. Kallos (Ed.), Embryonic Stem Cells - Basic Biology to Bioengineering (pp. 333-346). Online: InTech.
2010 Wickman, G., Samuel, M., Lochhead, P., & Olson, M. (2010). The rho-regulated ROCK kinases in cancer. In K. van Golen (Ed.), The Rho GTPases in Cancer (pp. 163-192). USA: Springer.
Year Citation 2019 Strudwick, X. L., Adams, D. H., Pyne, N. T., Samuel, M. S., Murray, R. Z., & Cowin, A. J. (2019). SYSTEMIC DELIVERY OF ANTI-INTEGRIN alpha L ANTIBODIES REDUCE EARLY MACROPHAGE RECRUITMENT, INFLAMMATION AND SCAR FORMATION IN MURINE BURN WOUNDS. In WOUND REPAIR AND REGENERATION Vol. 27 (pp. A4). WILEY. 2018 Strudwick, X. L., Adams, D. H., Pyne, N. T., Samuel, M. S., Murray, R. Z., & Cowin, A. J. (2018). SYSTEMIC DELIVERY OF ANTI-INTEGRIN AL ANTIBODIES REDUCES EARLY MACROPHAGE RECRUITMENT, INFLAMMATION, AND SCAR FORMATION IN MURINE BURN WOUNDS. In WOUND REPAIR AND REGENERATION Vol. 26 (pp. A31). WILEY. 2016 Rath, N., Kadir, S., Morton, J. P., Pinho, A. V., Helbig, L., Julian, L., . . . Olson, M. F. (2016). ROCK kinases drive invasive pancreatic tumor growth. In CANCER RESEARCH Vol. 76 (pp. 4 pages). San Diego, CA: AMER ASSOC CANCER RESEARCH.
2012 Clarke, M., Jamieson, T., Steele, C., Olson, M., Samuel, M., Das, S., . . . Nibbs, R. (2012). Inhibition of neutrophil chemokine receptor CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. In IMMUNOLOGY Vol. 137 (pp. 190). Glasgow, SCOTLAND: WILEY-BLACKWELL.
Year Citation 2014 Masre, S. F., Samuel, M. S., Olson, M. F., & Greenhalgh, D. A. (2014). Inducible ROCK 2/ras(Ha) cooperation requires wound promotion to achieve malignancy in transgenic mouse skin carcinogenesis, whereas inducible ROCK 2/PTEN loss fails to achieve benign papilloma. Poster session presented at the meeting of CANCER RESEARCH. San Diego, CA: AMER ASSOC CANCER RESEARCH.
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